Transmembrane Segments Prevent Surface Expression of Sodium Channel Na(v)1.8 and Promote Calnexin-dependent Channel Degradation
文献类型：期刊论文
| 作者 | Li, QA; Su, YY; Wang, H; Li, L; Wang, QO; Bao, L |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
 |
| 出版日期 | 2010 |
| 卷号 | 285期号:43页码:32977-32987 |
| 通讯作者 | Bao, L (reprint author), 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,baolan@sibs.ac.cn |
| 英文摘要 | The voltage-gated sodium channel (Na-v) 1.8 contributes substantially to the rising phase of action potential in small dorsal root ganglion neurons. Na(v)1.8 is majorly localized intracellularly and its expression on the plasma membrane is regulated by exit from the endoplasmic reticulum (ER). Previous work has identified an ER-retention/retrieval motif in the first intracellular loop of Na(v)1.8, which prevents its surface expression. Here we report that the transmembrane segments of Na(v)1.8 also cause this channel retained in the ER. Using transferrin receptor and CD8 alpha as model molecules, immunocytochemistry showed that the first, second, and third transmembrane segments in each domain of Na(v)1.8 reduced their surface expression. Alanine-scanning analysis revealed acidic amino acids as critical factors in the odd transmembrane segments. Furthermore, co-immunoprecipitation experiments showed that calnexin interacted with acidic amino acid-containing sequences through its transmembrane segment. Overexpression of calnexin resulted in increased degradation of those proteins through the ER-associated degradation pathway, whereas down-regulation of calnexin reversed the phenotype. Thus our results reveal a critical role and mechanism of transmembrane segments in surface expression and degradation of Na(v)1.8. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | ENDOPLASMIC-RETICULUM-RETENTION ; II MEMBRANE-PROTEINS ; QUALITY-CONTROL ; NEUROPATHIC PAIN ; NMDA RECEPTOR ; SUBUNIT ; TRAFFICKING ; MOTIF ; PATHWAYS ; SIGNALS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000283048200035 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1096]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Li, QA,Su, YY,Wang, H,et al. Transmembrane Segments Prevent Surface Expression of Sodium Channel Na(v)1.8 and Promote Calnexin-dependent Channel Degradation[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2010,285(43):32977-32987. |
| APA | Li, QA,Su, YY,Wang, H,Li, L,Wang, QO,&Bao, L.(2010).Transmembrane Segments Prevent Surface Expression of Sodium Channel Na(v)1.8 and Promote Calnexin-dependent Channel Degradation.JOURNAL OF BIOLOGICAL CHEMISTRY,285(43),32977-32987. |
| MLA | Li, QA,et al."Transmembrane Segments Prevent Surface Expression of Sodium Channel Na(v)1.8 and Promote Calnexin-dependent Channel Degradation".JOURNAL OF BIOLOGICAL CHEMISTRY 285.43(2010):32977-32987. |
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